A method generally used for examining the behavior of a compound in vivo is using the compound labeled with an isotope(s) introduced thereto. Examples of the compound include nucleic acids such as DNA and RNA. As the isotope, the use of a stable isotope brings an attention because it does not affect living organisms.
In particular, synthesis of a nucleic acid having stable isotopes introduced thereto generally is carried out by introducing a stable isotope to a monomer beforehand, and then, synthesizing a polynucleotide using this monomer as a raw material. In order to detect the stable isotopes with high sensitivity, it is desirable that the polynucleotide contains a large number of stable isotopes. However, according to this method, in order to introduce a large number of stable isotopes, all the monomers having bases A, G, C, and T/U, respectively, need to be labeled with the stable isotopes. Thus, this method has a problem in that it requires a large amount of labor and cost.
As a method for introducing a stable isotope, there has been disclosed a method in which the ring in 2,2′-cyclouridine is opened with benzoic acid (PhC18O2H), and a hydroxy group having a stable isotope (—18OH) is introduced to the 2′-position of the sugar (Non-Patent Document 1). However, according to this method, it is only possible to label a nucleoside having a specific pyrimidine base, and nucleosides having other bases cannot be obtained.
The above-described problem in terms of labor and cost in labeling with a stable isotope occurs not only in labeling the nucleic acids but also in labeling low molecular weight compounds, such as pharmaceuticals and agricultural chemicals, for example.